title: The underlying toxicological mechanism of chemical mixtures: a case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum.
abstract: Intracellular chemical reaction of chemical mixtures is one of the main reasons that cause synergistic or antagonistic effects. However, it still remains unclear what the influencing factors on the intracellular chemical reaction are, and how they influence on the toxicological mechanism of chemical mixtures. To reveal this underlying toxicological mechanism of chemical mixtures, a case study on mixture toxicity of cyanogenic toxicants and aldehydes to Photobacterium phosphoreum was employed, and both their joint effects and mixture toxicity were observed. Then series of two-step linear regressions were performed to describe the relationships between joint effects, the expected additive toxicities and descriptors of individual chemicals (including concentrations, binding affinity to receptors, octanol/water partition coefficients). Based on the quantitative relationships, the underlying joint toxicological mechanisms were revealed. The result shows that, for mixtures with their joint effects resulting from intracellular chemical reaction, their underlying toxicological mechanism depends on not only their interaction with target proteins, but also their transmembrane actions and their concentrations. In addition, two generic points of toxicological mechanism were proposed including the influencing factors on intracellular chemical reaction and the difference of the toxicological mechanism between single reactive chemicals and their mixtures. This study provided an insight into the understanding of the underlying toxicological mechanism for chemical mixtures with intracellular chemical reaction.
authors.affiliation: State Key Laboratory of Pollution Control and Resource Reuse, College of Environmental Science and Engineering, Tongji University, Shanghai 200092, China; Department of Chemical and Environmental Engineering, Anyang Institute of Technology, Anyang 455000, China.
authors.forename: Dayong
authors.initials: D
authors.lastname: Tian
authors.forename: Zhifen
authors.initials: Z
authors.lastname: Lin
authors.forename: Xianghong
authors.initials: X
authors.lastname: Zhou
authors.forename: Daqiang
authors.initials: D
authors.lastname: Yin
mesh_terms: D000447:Aldehydes / Q000633:toxicity*; D045424:Complex Mixtures / Q000633:toxicity*; D004357:Drug Synergism; D016014:Linear Models; D008954:Models, Biological; D009570:Nitriles / Q000633:toxicity*; D010776:Photobacterium / Q000187:drug effects*; D021281:Quantitative Structure-Activity Relationship; D018675:Toxicity Tests / Q000379:methods*
chemical_list: D000447:Aldehydes; D045424:Complex Mixtures; D009570:Nitriles; C000945:dicyanmethane
keywords: Joint effect; Mixture toxicity; Quantitative relationship; Toxicological mechanism